Differential central effects of mineralocorticoid and glucocorticoid agonists and antagonists on blood pressure.
Systolic blood pressure was measured, using an indirect tail method, in conscious male rats at several time intervals after the intracerebroventricular injection of mineralo-and glucocorticoid agonists and antagonists. Intracerebroventricular administration of the antimineralocorticoid RU 28318 (10 ng) decreased blood pressure, while the antiglucocorticoid RU 38486 (10 ng) caused an increase, which was slower in onset and of longer duration. The effect of the antimineralocorticoid was maximal at 8 h and had disappeared after 24 h. The antiglucocorticoid had a significant effect 24 and 48 h after injection. Neither antagonist was effective when administered sc at the same dose (10 ng). Intracerebroventricular administration of aldosterone (10 ng) and the selective glucocorticoid agonist RU 28362 (10 ng) increased and decreased blood pressure, respectively. Corticosterone given intracerebroventricularly (10-100 ng) did not affect blood pressure unless the dose was increased to 1 microgram. Two weeks after adrenalectomy a decrease in blood pressure was observed when the rats were given 0.9% saline instead of water to drink. Replacement therapy with corticosterone (12.5-mg steroid pellet, sc) restored blood pressure to the level in the sham-operated controls. The chronically elevated level of circulating corticosterone produced by a 100-mg sc corticosterone pellet increased blood pressure. The 12.5-and 100-mg sc corticosterone pellets resulted in plasma corticosterone levels of approximately 3 and 20 micrograms/100 ml, respectively. Intracerebroventricular administration of the glucocorticoid and mineralocorticoid antagonists (10 ng) increased and decreased, respectively, the blood pressure of the adrenalectomized rats receiving corticosterone substitution. From these data we conclude that corticosteroids can affect the central regulation of blood pressure. The mineralo- and glucocorticoids have opposite effects, which differ in onset and duration. The mineralocorticoids increased blood pressure, whereas the glucocorticoid decreased it.
van den Berg
D T
DT
Rudolf Magnus Institute for Pharmacology, University of Utrecht, The Netherlands.
de Kloet
E R
ER
van Dijken
H H
HH
de Jong
W
W
D000315:Adrenalectomy; D000450:Aldosterone / Q000494:pharmacology; D000732:Androstanols / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001921:Brain / Q000187:drug effects / Q000502:physiology*; D003345:Corticosterone / Q000494:pharmacology; D005938:Glucocorticoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D007276:Injections, Intraventricular; D008297:Male; D015735:Mifepristone / Q000494:pharmacology; D000451:Mineralocorticoid Receptor Antagonists / Q000494:pharmacology; D008901:Mineralocorticoids / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D013148:Spironolactone / Q000031:analogs & derivatives / Q000494:pharmacology
D000732:Androstanols; D005938:Glucocorticoids; D000451:Mineralocorticoid Receptor Antagonists; D008901:Mineralocorticoids; D013148:Spironolactone; D015735:Mifepristone; D000450:Aldosterone; C049154:11,17-dihydroxy-6-methyl-17-(1-propynyl)androsta-1,4,6-triene-3-one; C041006:RU 28318; D003345:Corticosterone